Introduction to Retrosynthesis

At the beginning of each chapter, we've explored how life-changing compounds, such as CRIXIVAN and Enalapril, were designed and developed. These and other important pharmaceuticals are typically synthesized through a strategic process called retrosynthetic analysis. Retrosynthesis is like reverse-engineering a layered cake: if you have a beautifully complex cake with multiple layers, you can think backward to identify the simpler ingredients needed to build the final cake.  The retrosynthetic arrow (typically depicted as a double-headed arrow pointing backward, like “⇒”) is a unique symbol in organic chemistry used to indicate retrosynthetic analysis. Unlike the regular reaction arrow (→), which represents the direction of a chemical transformation from reactants to products, the retrosynthetic arrow signifies the opposite: a conceptual backward-thinking process. It implies that we are breaking down a complex target molecule into simpler precursors rather than carrying out an actual reaction.  Here is our a three layer cake retrosynthetic analysis.

In retrosynthesis, chemists break down a complex molecule into simpler, more manageable starting materials, envisioning a synthetic path step by step. By deconstructing a molecule in this way, they can plan an efficient and practical route to construct the desired compound. To illustrate this, we’ll start with a simple example and then revisit how a key transformation—from Enalaprilat to Enalapril—was strategically developed to improve drug efficacy and bioavailability.